Is At1001 The Answer? (celiac Research)

[Claire]

This is about the drug being developed for the treatment of celiac and other autoimmune diseases.

Is AT1001 the Answer? (from Celiac Disease: Living Gluten Free)

Alessio Fasano, MD, was recently appointed director of the new Mucosal Biology Research Center at the University of Maryland, of which the university’s Center for Celiac Research (CFCR) is an integral part. Fasano, who also directs CFCR, reports that a multidisciplinary group of researchers at the two entities is collaborating to advance knowledge about autoimmunity within the context of celiac disease.

“Our team is convinced that celiac disease is the best disease model for studying basic autoimmunity because we have luxuries with celiac disease that we don’t have with other diseases,” Fasano says. “We know some of the genes involved; we know tissue transglutaminase is the antigen that is the object of the autoimmune response [the protein the body mistakes as foreign]; we know the small intestine is the primary target organ; and most importantly, we know the environmental trigger that leads to the autoimmune process is gluten.”

Fasano explains that under normal circumstances, large molecules like gluten are prevented from entering the body by a formidable barrier that covers the entire intestine. The barrier is a single layer of cells, and the spaces between the cells are tight junctions, dynamic structures that can be conceptualized as gates that open and close.

But what is the key, and when does the key open the gate, and why?

A few years ago, Fasano’s team discovered the key—the protein zonulin, which regulates the opening and closing of the gates and controls gut permeability. “Around the same time, we also determined that most of the autoimmune diseases are characterized by an extremely permeable intestinal wall and that individuals [with impaired immune function], particularly those with diabetes and celiac disease, have abnormally high zonulin levels,” Fasano explains. “Our next task, of course, was to find a way to inhibit the zonulin.”

It didn’t take long for the Fasano team to find an inhibitor and to develop an animal model for testing. Using diabetes-prone rats, the researchers evaluated the effectiveness of the zonulin peptide inhibitor AT1001. The rats were randomized to two groups—one group that received the inhibitor in their drinking water on a daily basis and an untreated control group. Eighty percent of the untreated rats developed diabetes, compared with only 26 percent of the treated rats.

“We know these animals developed diabetes because they leak in their gut, and they leak in their gut because of out-of-control zonulin,” Fasano says. “If you stop the leak by preventing the unusually high level of zonulin from interacting with its target receptor on intestinal cells, you will prevent diabetes.”

The plan now is to test the inhibitor in humans, Fasano states, specifically in individuals with celiac disease. “You would take a pill that contains the inhibitor and 15 minutes later eat some pizza or a Big Mac. The gluten in the food would cause a huge amount of zonulin to be released, but by the time it reached the target, the target would be blocked, and the intestine would not leak. The gluten would remain in the intestine until completely digested and would not have access to the immune system.”

http://abilitymagazine.com/celiac.html

[FaithInScienceToo]

Hi Claire,

Thanks for this post!

Hope you're having a good day -

Gina

[ravenwoodglass]

This is about the drug being developed for the treatment of celiac and other autoimmune diseases.

Is AT1001 the Answer? (from Celiac Disease: Living Gluten Free)

Alessio Fasano, MD, was recently appointed director of the new Mucosal Biology Research Center at the University of Maryland, of which the university’s Center for Celiac Research (CFCR) is an integral part. Fasano, who also directs CFCR, reports that a multidisciplinary group of researchers at the two entities is collaborating to advance knowledge about autoimmunity within the context of celiac disease.

“Our team is convinced that celiac disease is the best disease model for studying basic autoimmunity because we have luxuries with celiac disease that we don’t have with other diseases,” Fasano says. “We know some of the genes involved; we know tissue transglutaminase is the antigen that is the object of the autoimmune response [the protein the body mistakes as foreign]; we know the small intestine is the primary target organ; and most importantly, we know the environmental trigger that leads to the autoimmune process is gluten.”

Fasano explains that under normal circumstances, large molecules like gluten are prevented from entering the body by a formidable barrier that covers the entire intestine. The barrier is a single layer of cells, and the spaces between the cells are tight junctions, dynamic structures that can be conceptualized as gates that open and close.

But what is the key, and when does the key open the gate, and why?

A few years ago, Fasano’s team discovered the key—the protein zonulin, which regulates the opening and closing of the gates and controls gut permeability. “Around the same time, we also determined that most of the autoimmune diseases are characterized by an extremely permeable intestinal wall and that individuals [with impaired immune function], particularly those with diabetes and celiac disease, have abnormally high zonulin levels,” Fasano explains. “Our next task, of course, was to find a way to inhibit the zonulin.”

It didn’t take long for the Fasano team to find an inhibitor and to develop an animal model for testing. Using diabetes-prone rats, the researchers evaluated the effectiveness of the zonulin peptide inhibitor AT1001. The rats were randomized to two groups—one group that received the inhibitor in their drinking water on a daily basis and an untreated control group. Eighty percent of the untreated rats developed diabetes, compared with only 26 percent of the treated rats.

“We know these animals developed diabetes because they leak in their gut, and they leak in their gut because of out-of-control zonulin,” Fasano says. “If you stop the leak by preventing the unusually high level of zonulin from interacting with its target receptor on intestinal cells, you will prevent diabetes.”

The plan now is to test the inhibitor in humans, Fasano states, specifically in individuals with celiac disease. “You would take a pill that contains the inhibitor and 15 minutes later eat some pizza or a Big Mac. The gluten in the food would cause a huge amount of zonulin to be released, but by the time it reached the target, the target would be blocked, and the intestine would not leak. The gluten would remain in the intestine until completely digested and would not have access to the immune system.”

http://abilitymagazine.com/celiac.html

<{POST_SNAPBACK}>

Thanks, it would be nice if they found a pill for this. Without doubt it will need careful monitoring ($$$$$$$$) and be quite expensive but at least then Dr. may look for gluten sensitivities. It's apparently not profitable enough for them to diagnose in this country.

[gluttenfree]

I think this news is amazing...

As a newly diagnosed celiac, I am keeping my fingers crossed in regards to this research.

Think about what this would mean to celiacs as a community.

[VioletBlue]

But one has to wonder what is the downside of playing with the body's natural processes like that? What's the trade off in suppressing any part of the system from working the way it's designed to? I'm sorry but I just don't see the point in playing western medicine's trade off game anymore. I don't want to take a drug and ten years down the road find out there were long term side effects, or take a drug that allows me to eat pizza only to find out it has some other side effect like headaches or constipation or dry mouth or dizziness or who knows what else.

It's easier and safer to just not eat gluten.

violet

[Betty in Texas]

I agree with you no pills for me I don't trust the drug companys are the drs I think these drs get people on to much pills and they love to write those precriptions. They would' tell you that really all you need is a good diet and some multi vits no that would' bring in enough money. People get's on all this crap and feels worse and goes back to the dr again well lets change your medicine again again and they still feel like crap. So don't listen to every thing they say they don't know it all. My Mother is 92 they are always wanting to change her blood presure meds I said no it works fine why do you want to change well ok and also they are always wanting to put on colestrol meds well she has tryed it twice and feel so bad so I said why do you want to put her on meds that makes her so sick. She is 92 let her alone she only takes blood presure and baby asprune a day . And she is healtly and walks over my house everyday and wants to know where are we going today .

[Guest Doll]

But one has to wonder what is the downside of playing with the body's natural processes like that? What's the trade off in suppressing any part of the system from working the way it's designed to? I'm sorry but I just don't see the point in playing western medicine's trade off game anymore. I don't want to take a drug and ten years down the road find out there were long term side effects, or take a drug that allows me to eat pizza only to find out it has some other side effect like headaches or constipation or dry mouth or dizziness or who knows what else.

It's easier and safer to just not eat gluten.

violet

I just have to point out that in people predisposed to autoimmune diseases (Childhood (Type 1) Diabetes, Celiac Disease, MS, etc.), their body is *not* functioning normally. They have the genetics for these diseases and a leaky gut that is letting in triggers that cause these diseases to appear. This pill would stop a root cause of autoimmunity, which in my opinion, is a very good thing. Being gluten free may *help* the leaky gut, but it does not *stop* it or change genetics (many people go on to develop other autoimmune diseases and non-gluten food intolerances).

Many people with Celiac still have intestinal damage even while gluten-free (up to 40% I have heard), and many more have other autoimmune diseases. The gluten-free diet is a treatment, not a cure, and it does not stop the root cause of Celiac Disease. Fixing the leaky gut is a huge deal.

I personally don't want to run the risk of seizures (low blood sugar) when I am accidentally CC'd. I don't want to keep getting more autoimmune diseases. I don't want to have sub-clinical intestinal damage if I don't have to. People here with Refractory Celiac who may be reacting to the trace amounts of gluten we can never remove would love a better treatment than the gluten-free diet.

I think it is a choice, but there are very valid reasons for this pill, and this research. I personally am very excited about it, and I feel I have nothing to lose by taking it. I likely produce excess zonulin, and this pill will return my zonulin levels to normal. In this case, medication may be prefered over the diet if it fixes (one of) the problem(s) that caused the disease in the first place.

I agree that meds are often given out *way* too much (i.e. giving someone meds for "mild" Type 2 diabetes instead of having them lose weight through diet and exercise), but AT-1001 sounds like a case where the benefit DOES outweigh any risk. That said, there may not even be any.

If anyone here has entered trials for AT-1001, let me know. I actually applied and at first I was refused because I already had Type 1 diabetes. Then they called back and decided to accept me. However, I could not afford the last minute $2000 airfare down to the US for the screening.

If anyone has actually tested it, please let me know! Thanks!

P.S. AT-1001 will (in theory) help prevent/treat ALL autoimmune dieases, not just Celiac.

[julia6476]

I just have to point out that in people predisposed to autoimmune diseases (Childhood (Type 1) Diabetes, Celiac Disease, MS, etc.), their body is *not* functioning normally. They have the genetics for these diseases and a leaky gut that is letting in triggers that cause these diseases to appear. This pill would stop a root cause of autoimmunity, which in my opinion, is a very good thing. Being gluten free may *help* the leaky gut, but it does not *stop* it or change genetics (many people go on to develop other autoimmune diseases and non-gluten food intolerances).

Many people with Celiac still have intestinal damage even while gluten-free (up to 40% I have heard), and many more have other autoimmune diseases. The gluten-free diet is a treatment, not a cure, and it does not stop the root cause of Celiac Disease. Fixing the leaky gut is a huge deal.

I personally don't want to run the risk of seizures (low blood sugar) when I am accidentally CC'd. I don't want to keep getting more autoimmune diseases. I don't want to have sub-clinical intestinal damage if I don't have to. People here with Refractory Celiac who may be reacting to the trace amounts of gluten we can never remove would love a better treatment than the gluten-free diet.

I think it is a choice, but there are very valid reasons for this pill, and this research. I personally am very excited about it, and I feel I have nothing to lose by taking it. I likely produce excess zonulin, and this pill will return my zonulin levels to normal. In this case, medication may be prefered over the diet if it fixes (one of) the problem(s) that caused the disease in the first place.

I agree that meds are often given out *way* too much (i.e. giving someone meds for "mild" Type 2 diabetes instead of having them lose weight through diet and exercise), but AT-1001 sounds like a case where the benefit DOES outweigh any risk. That said, there may not even be any.

If anyone here has entered trials for AT-1001, let me know. I actually applied and at first I was refused because I already had Type 1 diabetes. Then they called back and decided to accept me. However, I could not afford the last minute $2000 airfare down to the US for the screening.

If anyone has actually tested it, please let me know! Thanks!

P.S. AT-1001 will (in theory) help prevent/treat ALL autoimmune dieases, not just Celiac.

Hello Doll--

This post was a while ago, but if you're still interested, I just registered to be part of the Phase 2 part of the study for AT-1001. I'm very excited and hopeful that it will help. Feel free to email me if you would like to chat!

Julie

[Generic]

I participated in the study a year ago. I started in Nov. had to stop Dec. 24th due to a diseased galllbladder. I found out that I was recieving the actual test drug (not a placebo) and wheat flour in capsules. I am a person who is super sensitive and reacts horribly to gluten and I DID NOT get sick! Not even once! Hooray!

I had a three reasons to make myself a guinea pig. I was diagnosed 21 years ago and never in this life expected for them to come up with any sort of pill, shot or whatever to help with celiac. It was considered extrememly rare back then.

* I wouldn't take any pill on a regular basis, but would like a safeguard against cc.

* Think of all the awareness a pill would bring. (think "IBS" pills or lactose intolerance pills, etc. Most people never heard of it before there was a pill.

* I was willing to sacrifice myself for idiots like my dad and sister (sister has since gluten-free). My dad is litteraly killing himself because he refuses to give up gluten.

If you have any questions let me know.

[Generic]

I had a GI Dr. call me this morning from Virignia Mason (the hosp. where I particpated in the study). He told me that the phase I participated in went so well that the new study is focusing on using the At-1001 on newly diagnosed Celiac paitents. They want to know if it helps them heal faster.

Just thought I would pass along the info.

[jerseyangel]

Generic,

Thanks for sharing this with us

[Generic]

I have hope that there will be something available within in the next 5 to 10 years. I just hope it happens before it is too late for my idiot dad.

If anyone at all has questions about participating let me know here or send me a pm.

I'll be happy to help.

[julia6476]

I participated in the study a year ago. I started in Nov. had to stop Dec. 24th due to a diseased galllbladder. I found out that I was recieving the actual test drug (not a placebo) and wheat flour in capsules. I am a person who is super sensitive and reacts horribly to gluten and I DID NOT get sick! Not even once! Hooray!

I had a three reasons to make myself a guinea pig. I was diagnosed 21 years ago and never in this life expected for them to come up with any sort of pill, shot or whatever to help with celiac. It was considered extrememly rare back then.

* I wouldn't take any pill on a regular basis, but would like a safeguard against cc.

* Think of all the awareness a pill would bring. (think "IBS" pills or lactose intolerance pills, etc. Most people never heard of it before there was a pill.

* I was willing to sacrifice myself for idiots like my dad and sister (sister has since gluten-free). My dad is litteraly killing himself because he refuses to give up gluten.

If you have any questions let me know.

Thank you for sharing your experience! I'm going for my initial consult appt. on 12/8. I'm very excited about possibly helping life be a little easier for all of us (even if it IS just to protect against CC.) I'm excited that there doesn't seem to be any side-effects, either. And that's GREAT that you didn't get any reaction to the gluten-containing pill!

I'll write more after I talk to them if people are interested. Thanks again!

[rinne]

Interesting, thanks for posting it.

I won't be going anywhere near it. I have zero trust in them.

I read recently that the original SCD (Dr.Haas)was used on Celiacs with great success many years ago but that at some point the shift was toward retricting gluten.

During the next few years, Dr. Haas treated over 600 cases of celiac disease with his Specific Carbohydrate Diet, maintaining his patients on it for at lease twelve months, and found that the prognosis of celiac disease was excellent. "There is complete recovery with no relapses, no deaths, no crisis, no pulmonary involvement and no stunting of growth."

In 1951, Dr. Haas, together with his son, Dr, Merrill P. Haas, published The Management of Celiac Disease, the most comprehensive medical text that had ever been written on celiac disease. With 670 references to published research, the book described celiac disease more completely than had ever been done before.

[email=http://www.scdiet.com/biography.html]

Sorry, don't know why my link didn't work.

I bolded the "complete recovery".

How is it that current gastroenterologists miss this? I would suggest their loyalty is to the pharmaceutical companies not their patients, they are drug pushers not healers.

I listened to a CBC program the other day about a drug prescribed for second stage diabetes, ten years ago doctors saw a connection to heart attacks in their patients but when they approached the company with their concerns they were intimidated and backed off. No mention that diet can control second stage diabetes. Now we know many people have died because of this drug. Last year it was the arthritis drug, and the drug companies scored big when they got the U.S. government to mandate Gardesil for young girls, I could go on and on and on ......

A general apology to those who should not be included in such a big sweep, I know there are good doctors.

[Generic]

I agree drugs are pushed way too much. I stand by why I participated.

It is in hope of raising awarness, hoping they can give my dad a pill that will help him to not slowly kill himself, and cc issues.

[rinne]

I agree drugs are pushed way too much. I stand by why I participated.

It is in hope of raising awarness, hoping they can give my dad a pill that will help him to not slowly kill himself, and cc issues.

And I get that there are lots of people who would benefit from a drug given a lifetime of living one way, I hope that if they proceed with this it will genuinely help your dad. I simply fear that, given their track record, for all the benefits there may be a down side that could be prevented jus by our changing our mind about what we eat.

[cyberprof]

I had a GI Dr. call me this morning from Virignia Mason (the hosp. where I particpated in the study). He told me that the phase I participated in went so well that the new study is focusing on using the At-1001 on newly diagnosed Celiac paitents. They want to know if it helps them heal faster.

Just thought I would pass along the info.

Generic, I am sending you a PM.

~Laura

[julia6476]

On Monday, I went for my initial consult with the doctor that would be conducting the Clinical Trial in my area. He went though my medical history, and then I met with a woman from Alba Therapeutics to go over more questions. I had an EKG, blood work, and had to give urine. But everyone was very nice and explained everything, and I felt very comfortable and excited. One downside is that you have to have a baseline endoscopy (even though I had one relatively recently in February) so that is rather invasive. But I understand why they need it.

So a few minutes ago, I got a phone call from the woman from Alba. She said my labs were TOO GOOD (meaning I've been doing TOO WELL on the gluten-free diet) and I've been disqualified from the study! I can't believe it. I had my records sent over, so they know that I have to potential for sky high levels. I feel like I've been punished for being good!

Oh well... at least I don't have to have that endoscopy again.

[Generic]

When I participated I didn't have to do a scope. They must be really getting down to the nitty gritty of this. Did they say whether or not the scope is done before or after the study meds? Just curious...

[julia6476]

When I participated I didn't have to do a scope. They must be really getting down to the nitty gritty of this. Did they say whether or not the scope is done before or after the study meds? Just curious...

In the study that I was supposed to be part of, there had to be TWO scopes. One at the beginning of the study and one at the end...

[Moony]

Does anybody know how the development is going. What I could read at clinical trials phase 2b was not successfull. Please give me an update.

[bincongo]

I had a GI Dr. call me this morning from Virignia Mason (the hosp. where I particpated in the study). He told me that the phase I participated in went so well that the new study is focusing on using the At-1001 on newly diagnosed Celiac paitents. They want to know if it helps them heal faster.

Just thought I would pass along the info.

I know there are problems with any new drug but I am a new Celiac and I would like to be part of this study. How do I get the information?

[chasbari]

But one has to wonder what is the downside of playing with the body's natural processes like that? What's the trade off in suppressing any part of the system from working the way it's designed to? I'm sorry but I just don't see the point in playing western medicine's trade off game anymore. I don't want to take a drug and ten years down the road find out there were long term side effects, or take a drug that allows me to eat pizza only to find out it has some other side effect like headaches or constipation or dry mouth or dizziness or who knows what else.

It's easier and safer to just not eat gluten.

violet

After my first blush reaction of a glimmer of hope.. and I am the ultimate skeptic.. I settled down to reality and can only say "Amen!' to the above. Ameliorating symptoms is what delayed the proper diagnosis in the first place.. "Western Medicine's trade off game." I reserve the right to use that phrase over and over. So right on!

[Des Carey]

Is there any update to this please?